Building Immunity

The foal’s immune system is almost a blank slate at birth; researchers are figuring out how to best protect horses as they grow.

The process of building immunity against disease-causing pathogens for a horse begins with a foal's first sip of colostrum after birth. Foals are born without much protection against the world outside the uterus. The mare's immune system develops antibodies against what she has encountered in the environment, plus what humans have vaccinated her against during her pregnancy. She passes those antibodies to the foal via the colostrum.

The maternal antibodies circulating in the foal's bloodstream gradually diminish as the foal gets older. Fortunately, as the foal ages its own immune system begins to mature and the foal begins producing his own antibodies. Researchers have sought to learn at what point in a young horse's life vaccinations against various diseases will be most beneficial, and they've tried to determine what other steps might be taken to enhance the immune system.

These are not easy questions to answer. Yes, there are sophisticated vaccines on the market today that help build immunity against certain pathogens. But in some cases, if the vaccines are given too early, the maternal antibodies can conflict with the vaccination's protective properties and prevent the vaccine from protecting the young horse fully.

Early Immunity

Before we delve into the latest research, we should make sure we understand terms that will crop up in the discussion:

Antibodies These are protein molecules produced by plasma cells. Antibodies are found in many body fluids, but they are most concentrated in blood serum. They have the ability to bind specifically to an invading antigen and destroy it. An antigen is any foreign substance that stimulates an antibody response, such as a bacterium, virus, or parasite.

Lymphocytes These are the cells that govern the body's immune response.

Phagocytes These are large white blood cells that can engulf/ingest invaders such as the aforementioned bacteria and viruses.

Macrophage A macrophage is a phagocytic tissue cell that can be fixed or freely motile. It functions to protect the body against infection and noxious substances.

Cytokines These are molecules that the immune system uses for communication. Cytokines deliver specialized messages to organize the way the immune system gathers up its forces to fight off an invader.

Receptor genesThese are a complex series of genes that get involved in developing a response when the body is invaded. Among the most important are T cell lymphocytes.

These are very basic descriptions of some of the complex immune system's components. We should understand that immunology is a developing science, but it has its roots in antiquity. Way back in 430 B.C. Thucydides, the historian of the Peloponnesian war, wrote that only those who had recovered from the plague should nurse the sick because they would not contract the disease.

The Chinese, well before the birth of Christ, were also aware of this phenomenon. They observed that people who survived smallpox were never afflicted again. In their own way they invented vaccination. They deliberately infected infants with smallpox by rubbing the scabs from an infected individual into small cuts in the skin of those who had not contracted the disease. This worked in a number of instances, but not always. The death rate was high. Then, the Chinese realized that if they used material from individuals who had only a mild form of smallpox, the mortality rate decreased dramatically.

It wasn't until 1798 when Edward Jenner, an English physician, discovered that material from lesions in cases of cowpox, a form of cattle disease in Europe at the time, could be substituted for smallpox in inoculations against smallpox.

Then along came Louis Pasteur. By a quirk of fate he discovered that killed bacteria could create immunity against disease. Killed organisms were unable to cause the disease, but they stimulated the immune system to react so the animal or person became immune to future attacks.

Pasteur was studying the resistance of chickens to fowl cholera, a deadly bacteria-based affliction. Pasteur had a culture of this organism that was accidentally allowed to "age" on a laboratory shelf while his assistant went on vacation. When the assistant returned, he attempted to infect chickens involved in the experiment with the aged culture. It didn't work. The birds did not contract cholera. Later when they tried to infect the same chickens with a fresh culture, the chickens did not get the disease. The killed culture had stimulated the immune system to act, and the chickens were immune to cholera.

Pasteur was the first to refer to the process as vaccination. (Vacca is Latin for cow. Thus, Pasteur's use of the terms vaccine and vaccination appear to be in honor of the work Jenner had carried out with cowpox.)

Most of what is known about the immune system came to light in the past 70 or so years. Antibodies weren't discovered until in the 1930s, and in the 1950s scientists determined that lymphocytes were the cells that govern the immune response. It wasn't until 1966 that the antibody IgE, which is responsible for allergic reactions, was discovered.

Researchers have since learned to produce safe vaccines by, in effect, "killing" the disease-causing organism (as had happened by accident in Pasteur's early work). These are called killed virus vaccines. There also are modified-live vaccines, in which the pathogen must be robust enough to replicate in the animal and stimulate the immune system, but weak enough that it doesn't make the horse sick. Researchers in recent years have developed vectored vaccines for horses, which rely on an organism (vector) that carries foreign genes into the horse without causing disease itself. Today's scientists are adding still another exciting concept in the development of vaccines--bioengineering with DNA material.

Today's Research

The above history of immunity and vaccination sets the stage for a discussion of the latest advances in the complex field of equine immunology research. The goal of neonatal research in this realm has been to find ways to enhance the foal's immune system so the animal is protected from infectious diseases during those vulnerable first days, weeks, and months.

For example, Tracy Sturgill, DVM, of the University of Kentucky's Gluck Equine Research Center in Lexington, reported at the 2008 American Association of Equine Practitioners (AAEP) Convention on research aimed at determining whether vaccination against influenza at an early age would be beneficial to a foal. Sturgill said foals get all of their maternally derived antibodies from ingesting colostrum. While these maternal antibodies work to the foal's health advantage, she said there could be drawbacks, such as antibodies from the mare sometimes interfering with the production of antibodies in the foal.

In the Gluck study, foals born to mares vaccinated against influenza were themselves vaccinated beginning at 1 month of age with an inactivated equine influenza vaccine, a vectored vaccine, or no vaccine. Researchers challenged the foals at 5 months of age with equine influenza virus, measuring and recording clinical signs and post-challenge antibodies. Researchers also involved vaccinated (inactivated vaccine only) and nonvaccinated yearlings in the influenza challenge in order to compare the results in the foals. Sturgill reported: All foals had high maternal antibodies to equine influenza before vaccination. Both vaccines failed to induce an increase in hemagglutinin inhibition (HI) titers, a measure of antibody production, in the foals. After challenge with equine influenza virus there were no significant differences between the vaccinated and control foals in terms of clinical response, virus secretion, or antibody production.

By contrast, the vaccinated yearlings responded to the vaccine and were protected from the challenge. All groups developed an antibody response post-infection. While the foals were not fully protected, the signs of clinical infection were less severe than in the nonvaccinated yearling group.

Sturgill noted that vaccinating foals for influenza in the presence of maternal antibodies neither increased the foals' antibody response, nor worsened their response to clinical infection. So, while vaccinating during the neonate period was not helpful, it wasn't harmful either, and it might be of benefit when the vaccination status of the mare is unknown.

In another AAEP Convention report from the Gluck Center, David Horohov, PhD, reported that vaccinating 5-month-old foals with a single dose of a West Nile virus chimeric vaccine (created by replacing the structural genes of the attenuated human yellow fever vaccine with the structural genes of West Nile virus) in the presence of maternal antibodies to West Nile virus did induce a beneficial cell-mediated response.

"The response is indicative of an immunologically protectve Th-1 response with stimulation of cytoxic T lymphocytes," noted Horohov.

Noah Cohen, VMD, of Texas A&M University, reported at that AAEP meeting on studies in which scientists examined ways to improve a foal's immune response to infection. Cohen explains the research this way: "Immune responses may be categorized as innate or adaptive. Adaptive responses include those that involve recognition and memory of specific stimuli (such as proteins of bacteria or viruses) by immune cells (including lymphocytes). Stimulation of adaptive immunity is the basis for vaccines. Adaptive responses require days to weeks for stimulation."

On the other hand, Cohen notes, "Innate immunity involves nonspecific responses of the host to infection. Stimuli of innate immune responses include things like endotoxin and bacterial DNA. It is known that small bits of DNA with certain patterns can stimulate innate immune responses. There are small bits of DNA known as CpGs that can be synthesized in the laboratory. Synthetic CpGs are used in vaccines to improve the overall immune response to vaccine." Past experience with CpGs has proven they are safe and effective when included in vaccines for various species, he says.

Research has shown that synthetic CpGs might be useful to enhance immune responses of foals.

His research was designed to determine whether CpGs would be effective in stimulating the immune cells of young foals. Here is what Cohen said about research involving five foals: "We found these CpGs are effective at stimulating immune cells of very young foals, suggesting that CpGs should be further evaluated as a way to improve the immune response of newborn foals to help protect them against bacterial infections, such as Rhodococcus equi (the leading cause of foal pneumonia)."

Cohen says work has continued on the project, and his team "has further substantiated the ability of synthetic CpGs to enhance immune responses of foals."

Also at the 2008 AAEP meeting Steeve Giguère, DVM, PhD, Dipl. ACVIM, of the University of Florida, discussed how R. equi-caused pneumonia is endemic on a number of farms. The goal of his research was to determine whether immunostimulants could decrease the incidence of respiratory disease by enhancing the immune system's ability to kill R. equi cells. Seventeen foals were involved in the study, and they received one of two immunostimulants on the market (either Zylexis or EqStim) or saline for the control group. Researchers infected cells from the foals in vitro (in laboratory samples) with R. equi.

The researchers concluded: "Neutrophils from foals treated with inactivated parapoxvirus ovis (Zylexis) had significantly greater ability to phagocytize (engulf) R. equi and undergo oxidative burst on Days 19 and 31 compared to baseline values. On Day 31, foals treated with inactivated parapoxvirus ovis had significantly greater phagocytosis and oxidative burst than foals treated with inactivated Propionibacterium acnes (EqStim). In contrast, treatment with EqStim resulted in significantly less intracellular proliferation of R. equi within blood- derived macrophages (R. equi multiplied less within these cells) compared to control foals, but not compared to foals treated with Zylexis."

In other words, treating neonatal foals' cells with immunostimulants enhanced the activity of neutrophils and macrophages after laboratory infection with R. equi.

Take-Home Message

Much has been uncovered about developing immunity in foals, but a great deal remains shrouded in mystery. How and when to vaccinate foals as maternal antibodies wane and their own immune systems kick into high gear will continue to be investigated. Maybe soon horse owners will know exactly when to give a vaccination to confer the greatest protection for a specific horse's needs, no matter its age.